It is estimated that approximately 1 million people suffer from IBD in the US, while at a European level there are approximately 2.5 million reported cases. Current immunosuppressive treatments (eg. thiopurines, anti-TNFa antibodies and corticosteroids) are limited, and have modest clinical efficacy, evidenced by the fact that up to 75% of patients with Crohn’s disease and 25% of those with ulcerative colitis will require surgery. This highlights the need for alternative anti-inflammatory treatment options which are well tolerated and have long term efficacy in patients. The study outlined in this proposal will address current claims that HO-1 inducers and linear tetrapyrroles are effective anti-inflammatories that have potential for use in preventative medicines or as therapeutics which could potentially complement current biologics used to treat IBD. A key advantage associated with the molecules that they are naturally derived products, one example being marine sourced phycocyanobilin. Indeed, many studies have reported that the consumption of blue green algae promotes immunity and protects against a range of inflammatory diseases such as colitis, arthritis, and allergic rhinitis in animals and humans. Our preliminary studies thus far have been very promising and our compounds of interest have shown clear effects on both innate and adaptive human immune cells. We have also identified a novel indole-based anti-inflammatory molecule from the parasite, T.brucei, which has huge potential as a novel drug candidate, given its ability to dampen inflammatory responses. Of note, indole based products have recently been highlighted as promising therapeutics for IBD and parasite derived products have long been explored as anti-inflammatories to treat a range of autoimmune and inflammatory diseases. Validation of these molecules of interest in IBD patient samples and in vivo IBD models will support future studies that could potentially lead to the development of new IBD therapies.
